Diuretic response in acute heart failure: clinical characteristics and prognostic significance

Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is
lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient
characteristics and relationships with outcome.
Methods and results
We examined diuretic response (defined as D weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure
patients from the PROTECT trial. Day 4 responsewas used to allow maximum differentiation in responsiveness and tailoring
of diuretic doses to clinical response, following sensitivity analyses.We investigated predictors of diuretic response
and relationships with outcome. The median diuretic responsewas20.38 (20.80 to 20.13) kg/40 mg furosemide. Poor
diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and
atherosclerotic disease (all P , 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42;
95% CI: 1.11–1.81, P ¼ 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14–
1.59, P , 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24–2.01, P , 0.001) in multivariable models.
The proposed metric—weight loss indexed to diuretic dose—better captures a dose–response relationship. Model
diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared
with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily
interpreted signal.
Conclusions Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic
disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc,
hypothesis-generating study.